糖尿病為慢性新陳代謝疾病，民國90年行政院衛生署十大死因調查中，糖尿病排名第五位，有研究顯示，糖尿病病患較正常人容易遭受細菌的入侵，並且引發敗血症(Donder，2002)，又因敗血症所引起的多器官功能衰竭以呼吸系統衰竭最為普遍，其死亡率可高達60%，所以本研究主要是探討敗血症對於糖尿病老鼠肺部防禦機轉之影響及其造成肺部傷害的作用。我們將BABL/c老鼠以Streptozotocin(STZ)誘發成糖尿病鼠，分別於8週及30週比較兩組老鼠血糖值，結果顯示本實驗成功的誘導形成糖尿病，並具有統計上之差異其P < 0.001；於老鼠32週齡時，使用盲腸結紮穿刺手術模式，誘導老鼠產生敗血症，於手術後20小時，經由肺泡灌流技術分離出老鼠肺泡巨噬細胞，利用流式細胞儀及DAPI染色法偵測肺泡巨噬細胞凋亡比例，結果顯示糖尿病老鼠在未感染下，肺泡巨噬細胞凋亡比例與健康老鼠相當；但一旦引發敗血症，細胞凋亡比例以流式細胞儀偵測結果顯示，敗血症糖尿病老鼠誘發肺泡巨噬細胞凋亡比例約為敗血症正常血糖老鼠的1.5倍，而以DAPI染色結果約為未誘發敗血症健康老鼠的3倍。為了更進一步評估糖尿病老鼠誘發敗血症後，肺部清除細菌功能之影響，將術後20小時老鼠左肺取出進行均質，以無菌技術操作細胞培養18~24小時後，計算細菌之菌落數並將其作比較，結果顯示未誘發敗血症的糖尿病及控制組老鼠，肺部細菌量是無差異;誘導敗血症後，控制組老鼠肺部細菌量會提升為原來的846倍，糖尿病老鼠又比控制組來得高約91倍。由以上研究結果顯示敗血症對糖尿病老鼠肺部傷害是比較嚴重的，而敗血症造成健康老鼠及糖尿病老鼠肺部傷害之差異性機制，是值得我們更進一步去研究探討。; Sepsis could cause serious lung injuries, including cellular apoptosis and vascular leakage. These resulted deteriorations of lung defense might lead to an increased susceptibility to pulmonary infection. Diabetes mellitus (DM) is identified as an independent risk factor for the development of lower respiratory tract infections, for which the depressed cellular protection may play a role. Since alveolar macrophages (AM) represent the first line immune effector cells of the lung airspace, we hypothesized that, for DM subjects, septic AM apoptosis will be augmented, and thereafter, the lung will be prone to the development of pneumonia. In the present study, DM was successfully induced in BALB/c male mice by streptozotocin i.p. injection, achieving a blood sugar ≧ 250ml/dl at 8 wk. At 32 wk, mice were cecal-ligated and -punctured and then scarified 20 h later. AM were obtained and their apoptosis was greater in septic DM mice than in septic normal ones (24.9% ± 1.8% vs. 16.8% ± 2.82%, P < 0.05). The lung bacterial burden was increased 91 fold in diabetic septic mice than in septic normal ones. Consequently, the additional worsening of septic lung injury in diabetic individuals could instigate a superimposed lung infection and/or respiratory failure.
